Combination of adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes for protecting kidney from acute ischemia-reperfusion injury

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• 作者：Kun-Chen Lin^a ; ¹ ; Hon-Kan Yip^b ; ^c ; ^d ; ^e ; ^f ; ¹ ; Pei-Lin Shao^f ; Shun-Cheng Wu^g ; Kuan-Hung Chen^a ; Yen-Ta Chen^h ; Chih-Chao Yangⁱ ; Cheuk-Kwan Sun^j ; Gour-Shenq Kao^b ; Sheng-Yi Chen^b ; Han-Tan Chai^b ; Chia-Lo Chang^k ; Chih-Hung Chen^l ; Mel S. Lee^m ; ^{mellee@cgmh.org.tw" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Acute kidney ischemia&ndash ; reperfusion injury ; Exosome ; Adipose-derived mesenchymal stem cell ; Inflammation ; Oxidative stress
• 刊名：International Journal of Cardiology
• 出版年：2016
• 出版时间：1 August 2016
• 年：2016
• 卷：216
• 期：Complete
• 页码：173-185
• 全文大小：3918 K

文摘

In this study, we tested the hypothesis that a combined adipose-derived mesenchymal stem cell (ADMSC) and ADMSC-derived exosome therapy protected rat kidney from acute ischemia–reperfusion (IR) injury (i.e., ligation of both renal arteries for 1 h and reperfusion for 72 h prior to euthanization).

Methods and results

Adult-male SD rats (n = 40) were equally categorized into group 1 (sham control), group 2 (IR), group 3 [IR + exosome (100 μg)], group 4 [IR + ADMSC (1.2 × 10⁶ cells)], and group 5 (IR-exosome-ADMSC). All therapies were performed at 3 h after IR procedure from venous administration. By 72 h, the creatinine level and kidney injury score were the lowest in group 1 and the highest in group 2, significantly higher in group 3 than in groups 4 and 5, and significantly higher in group 4 than in group 5 (all P < 0.0001). The protein expression of inflammatory (TNF-α/NF-κB/IL-1β/MIF/PAI-1/Cox-2), oxidative-stress (NOX-1/NOX-2/oxidized protein), apoptotic (Bax/caspase-3/PARP), and fibrotic (Smad3/TGF-β) biomarkers showed an identical pattern, whereas the anti-apoptotic (Smad1/5, BMP-2) and angiogenesis (CD31/vWF/angiopoietin) biomarkers and mitochondrial cytochrome-C showed an opposite pattern of creatinine level among the five groups (all P < 0.001). The microscopic findings of glomerular-damage (WT-1), renal tubular-damage (KIM-1), DNA-damage (γ-H2AX), inflammation (MPO/MIF/CD68) exhibited an identical pattern, whereas the podocyte components (podocin/p-cadherin/synaptopodin) displayed a reversed pattern of creatinine level (all P < 0.0001).

Conclusion

Combined exosome–ADMSC therapy was superior to either one for protecting kidney from acute IR injury.